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Dose-escalating Trial With Allo-RevCAR01-T Cells in Combination With CD123 Target Module (R-TM123) for Participants With Selected Hematologic Malignancies Positive for CD123

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05949125
Recruitment Status : Recruiting
First Posted : July 17, 2023
Last Update Posted : April 30, 2024
Sponsor:
Collaborator:
Allucent (NL) BV
Information provided by (Responsible Party):
AvenCell Europe GmbH

Brief Summary:
The Allo-RevCAR01-T-CD123 drug is a combination of a cellular component (Allo-RevCAR01-T) with a recombinant antibody derivative (R-TM123), which together form the active drug. The cellular component Allo-RevCAR01-T consists of an allogeneic human T-cell genetically multi-edited and expressing a reversed, universal chimeric antigen receptor (RevCAR) presenting an extracellular peptide epitope (RevCAR epitope). R TM123 functions as a bridging module between Allo RevCAR01-T and a CD123-expressing target cancer cell by selectively binding the RevCAR epitope and CD123.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia, in Relapse Acute Myeloid Leukemia Refractory Other: Cyclophosphamide (Non-IMP, Lymphodepletion) Other: Fludarabine (Non-IMP, Lymphodepletion) Drug: R-TM123 Drug: Allo-RevCAR01-T Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

Dose escalation follows a BOIN comb design with 3 dose levels of 100, 250, and 500 million Allo-RevCAR01-T and 3 dose levels of R-TM123 resulting in a maximum of 9 dose levels.

Given 1 participant dose level cohorts, there will be an inherent stagger between each participant equivalent to the DLT window of 28 days

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Open-label, Phase 1 Study of Allo-RevCAR01-T-CD123 Consisting of Genetically Modified T Cells Carrying Reverse Chimeric Antigen Receptors (Allo RevCAR01 T) in Combination With CD123 Target Module (R-TM123) for the Treatment of Patients With Selected Hematologic Malignancies Positive for CD123
Actual Study Start Date : January 3, 2024
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : June 2026


Arm Intervention/treatment
Experimental: Allo-RevCAR01-T-CD123 treatment
Following lymphodepleting therapy, R-TM123 will be administered as continuous infusion from Cycle 1 Day 1 and then will continue for 20 days. After 4 hours (±30 minutes) of R TM123 start on Day 1, a single dose of Allo-RevCAR01-T will be administered as IV infusion
Other: Cyclophosphamide (Non-IMP, Lymphodepletion)
Intravenous infusion over 3 days (d-5 to d-3)

Other: Fludarabine (Non-IMP, Lymphodepletion)
Intravenous infusion over 3 days (d-5 to d-3)

Drug: R-TM123
Intravenous infusion over 20 days
Other Name: R-TM123 is one component of the Allo-RevCAR01-T-CD123 treatment

Drug: Allo-RevCAR01-T
A single dose of Allo-RevCAR01-T will be administered as IV infusion on Treatment day 1. Allo-RevCAR01-T will not be administered again within this study.
Other Name: Allo-RevCAR01-T is one component of the Allo-RevCAR01-T-CD123 treatment




Primary Outcome Measures :
  1. To assess the safety profile of the treatment [ Time Frame: At the end of cycle 1 (in total 28 days, given no treatment interruptions) ]
    Incidence and intensity of adverse events (AEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), tumor lysis syndrome, and graft versus host disease (GvHD), which will be graded according to widely accepted specialized criteria

  2. To determine the incidence of dose-limiting toxicities (DLT) [ Time Frame: At the end of cycle 1 (in total 28 days, given no treatment interruptions) ]
    Incidence of DLTs

  3. To determine the maximum tolerated dose (MTD) [ Time Frame: At the End of Cycle 1 (in total 28 days, given no treatment interruptions) ]
    MTD


Secondary Outcome Measures :
  1. Evidence of biological and clinical activity including best response rate [ Time Frame: At any timepoint until end of study (6 months after the end of last R-TM123 administration) ]
    • Complete remission (CR, CRh, CRi, CRMRDneg, CRMRDpos)
    • Partial remission (PR)
    • Overall response rate (ORR)
    • Stable disease (SD)
    • Best response rate
    • Duration of response

  2. Survival rates [ Time Frame: At end of study visit (6 months after the end of last R-TM123 administration) ]
    • Progression free survival
    • Overall survival

  3. Response rate to consolidation treatment cycls [ Time Frame: At any timepoint until end of study (6 months after the end of last R-TM123 administration) ]
    • Complete remission (CR, CRc, CRh, CRi, CRMRDneg, CRMRDpos)
    • Morphologic leukemia free state (MLFS),
    • Partial remission (PR)
    • Overall response rate (ORR)
    • Stable disease (SD)
    • Best response rate
    • Duration of response

  4. Establishing recommended Phase 2 dose (RP2D) [ Time Frame: At any timepoint until end of study (6 months after the end of last R-TM123 administration) ]
    Based on assessments of MTD and DLTs



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants, age ≥18 years.
  2. HLA type of participant must match at HLA B and C loci
  3. Participants with CD123+ AML (defined as ≥20% of leukemic cells expressing CD123 at any point in the course of disease)

    - Participants with MRD+ AML are eligible but must meet specific criteria i. MRD positivity must be based on assays and markers supported by consensus guidelines [Heuser2021] and in the judgment of the investigator must confer negative prognostic risk highly likely to result in relapse.

    ii. Must have received or be ineligible for allogeneic stem cell transplant. iii. Must be approved by the Sponsor for inclusion in the study.

  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  5. Life expectancy of at least 3 months in the judgment of the investigator.
  6. Adequate renal and hepatic laboratory assessments:
  7. Adequate cardiac function
  8. Permanent venous access existing (e.g., port-system) or willing to have such a device inserted.
  9. Able to give written informed consent.
  10. Weight ≥45 kg.
  11. Negative pregnancy; routinely using a highly effective method of birth control

Exclusion Criteria:

  1. Acute promyelocytic leukemia (t15;17).
  2. AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma)
  3. Acute manifestationof AML in the central nervous system.
  4. Bone marrow failure syndromes
  5. Cardiac disease: heart failure (New York Heart Association III or IV); unstable coronary artery disease, myocardial infarction, or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within the last 6 months prior to study entry.
  6. Active pulmonary disease with clinically relevant hypoxia
  7. Parkinson's disease or epilepsy with clinical symptoms in the previous 12 months .
  8. Stroke, seizure, or intracranial hemorrhage in the past 12 months.
  9. History or presence of disseminated intravascular coagulation (DIC), deep vein thrombosis or thromboembolism within 3 months prior to start of treatment.
  10. Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
  11. Toxicity from prior anticancer treatment has not resolved to Grade ≤1 or baseline.
  12. Allogeneic stem cell transplantation within last 2 months or GvHD requiring immunosuppressive therapy.
  13. Vaccination with live viruses <2 weeks prior to lymphodepletion therapy.
  14. Major surgery within 28 days prior to start of R-TM123 infusion.
  15. Prior malignancy in the past 3 years or any malignancy requiring ongoing active therapy other than adjuvant endocrine therapy. Participants with resected or ablated tumors, such as basal cell carcinoma of skin, carcinoma-in-situ of the cervix, or other tumors considered cured by local treatment may be considered for the study with Sponsor approval.
  16. Treatment with any investigational drug substance or experimental therapy within 4 weeks or 5 half-lives (whichever is shorter) of the substance prior to lymphodepletion.
  17. Treatment with anti-leukemic therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to lymphodepletion.
  18. Prior treatment with gene modified cell products.
  19. Use of checkpoint inhibitors within 5 half-lives of the specific drug.
  20. Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants.
  21. Pregnant or breastfeeding women.
  22. Psychologic disorders with treatment modifications required within the last 3 months, drug and/or significant active alcohol abuse as per investigator's medical judgement. Depression or anxiety due to presence of the underlying malignancy may be exempted with Sponsor approval.
  23. History of human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
  24. Presence of autoantibodies against lupus La protein (La)/ Sjögren syndrome type B antigen (SS-B) or presence or history of autoimmune diseases associated with such antibodies
  25. Known hypersensitivity to cellular component (Allo-RevCAR01-T) and/or TM (R-TM123) excipients or to compounds of the lymphodepletion therapy, tocilizumab, or corticosteroids.
  26. Evidence that the participant is not likely or able to follow the study protocol (e.g., lacking compliance) in the judgment of the investigator.
  27. Participant unable to understand the informed consent and possible consequences of the participation in the clinical trial in the judgement of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05949125


Contacts
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Contact: Katja Jersemann, Dr. +493514466450 ext 0 AVC-201-01@avencell.com
Contact: Martina Raupach +493514466450 ext 0 AVC-201-01@avencell.com

Locations
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Germany
Universitätsklinikum Ulm Recruiting
Ulm, Baden-Württemberg, Germany, 89081
Contact: Elisa Sala, MD       elisa.sala@uniklinik-ulm.de   
Klinikum der Universität München Not yet recruiting
Munich, Bavaria, Germany, 81377
Contact: Marion Subklewe, Prof.       Marion.Subklewe@med.uni-muenchen.de   
Universitätsklinikum Würzburg Recruiting
Würzburg, Bayern, Germany, 97080
Contact: Chatterjee Manik, MD       Chatterjee_m@ukw.de   
Universitätsklinikum Marburg Recruiting
Marburg, Hessen, Germany, 35032
Contact: Stephan Metzelder, Prof.       metzelde@med.uni-marburg.de   
Universitätsklinikum Dresden Recruiting
Dresden, Sachsen, Germany, 01307
Contact: Martin Wermke, Prof.       martin.wermke@ukdd.de   
Charité Universitätsmedizin Berlin Recruiting
Berlin, Germany, 13353
Contact: Jörg Westermann, Prof.       joerg.westermann@charite.de   
Medizinische Hochschule Hannover Not yet recruiting
Hannover, Germany
Contact: Felizitas Thol, Prof.       Thol.Felicitas@mh-hannover.de   
Universitätsklinikum Köln Recruiting
Köln, Germany, 50937
Contact: Lukas Frenzel, PD       lukas.frenzel@uk-koeln.de   
Netherlands
Erasmus University Medical Center Not yet recruiting
Rotterdam, GD, Netherlands, 3015
Contact: Mojca Jongen-Lavrencic, Dr.       m.lavrencic@erasmusmc.nl   
Amsterdam University Medical Center Not yet recruiting
Amsterdam, HV, Netherlands, 1081
Contact: Arjan van de Loosdrecht, Prof.       a.vandeloosdrecht@amsterdamumc.nl   
University Medical Center Groningen (UMCG) Not yet recruiting
Groningen, RB Groningen, Netherlands, 9700
Contact: Gerwin Huls, Prof.       g.huls@umcg.nl   
Sponsors and Collaborators
AvenCell Europe GmbH
Allucent (NL) BV
Investigators
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Study Director: Tapan Maniar, MD AvenCell Europe GmbH
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Responsible Party: AvenCell Europe GmbH
ClinicalTrials.gov Identifier: NCT05949125    
Other Study ID Numbers: AVC-201-01
2022-501797-19-00 ( Other Identifier: EU CT Number )
First Posted: July 17, 2023    Key Record Dates
Last Update Posted: April 30, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
Neoplasms by Site
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists